PROJECT SUMMARY/ABSTRACT Mission and themes. This is an application for renewal of a George M. O'Brien Kidney Research Core Center at the University of Texas Southwestern Medical Center at Dallas currently directed by Dr. Orson Moe who is Professor of Internal Medicine and Physiology, and Chief of the Division of Nephrology at UT Southwestern. The overall mission of the Center is to promote bidirectional synergistic interactions between basic scientists and clinical researchers, maximally optimize research for renal investigators, and encourage and facilitate non-renal researchers to study renal questions. Our three main themes are: 1. Kidney development and genetics. 2. Physiology and pathophysiology. 3. Chronic kidney disease and its complications Need for Center. Discoveries in renal science is emerging at an alarming rate and from diverse circumstances. No single laboratory or investigator can take their findings through development into full biologic elucidation and eventual clinical applications. Researchers outside the renal field often make interesting findings pertinent to kidney disease but lack the ability to pursue the finding due to lack of knowledge, reagents, models, and techniques. This gap needs to be bridged so opportunities of discovery will not be missed, and we can also increase the number of renal investigators. Within the renal research community, basic scientists need appropriate and extensive phenotyping, to translate their findings to clinical application. Clinical researcher also need bench clarification of clinical findings to elucidation mechanisms, and robust systems to discover new biomarkers and treatment. Bidirectional translation is a central purpose of our Center. Our ultimate goal is to improve diagnosis and treatment of kidney diseases. Number of Center Members and Direct Cost. Our Center houses 12 Center Members, which are UT Southwestern faculty holding a title within and directly supported by the O'Brien Center. We have 254 Core Members, who are on or off campus users of the O'Brien Center. The direct cost requested is about $749,000 per year. The Center is subsidized by the Renal Division and by UT Southwestern so the real operating cost actually exceeds the allowed budget. Overview of research base, Biomedical Cores, P&F Program and Enrichment Program. The Center supports all research with some relationship to kidney function and disease. Many basic scientists work on highly fundamental biologic problems such as atherosclerosis, autophagy, cellular protein trafficking, diabetes, find scientific merit in using the kidney as model systems and we are delighted that we can attract such investigators to renal investigation. We fulfil our role via three portals- infrastructure support, education, and fiscal support to jumpstart pilot projects. Biomedical Research Cores. Four Cores are designed to provide the infrastructure to bridge the full span for bidirectional translation. (A) The Animal Core distributes and helps generate genetically modified mice as well as create disease models for full phenotyping by two other Cores. (B) The Physiology Core provides functional phenotyping enabling the study of a wide variety of whole organism function. (C) Cell Biology, Pathology, and Imaging Core supports anatomic and functional phenotyping from the whole organism to the single cell. (D) The Clinical Translational Core facilitates bidirectional translation of findings to fulfil our objective. Enrichment Program. We provide education through several means. We have a bimonthly seminar series with lecturers on campus as well as invited speakers to cover many aspects of kidney function and disease. In addition, we have an annual Symposium where specific topics are covered by leading experts in the field. Our Biomedical Cores also provide theoretically and technical training to investigators. Finally, our O'Brien Center hosts several summer projects to educate and motivate students to enter renal research. Pilot and Feasibility Program. In the preliminary phase of hypothesis testing, investigators frequently do not have adequate data for extramural grant application. Our P&F program funds two grants from junior investigators or senior investigators considering an excursion from their trajectory to venture into kidney research. We have an excellent track record of previous grantees submitting and obtaining grants. The mechanisms outlined serves a large body of investigators in the US and abroad to make advances in kidney development and genetics, physiology and pathophysiology, and chronic kidney disease, to advance the diagnosis and treatment of human kidney disease.